3-Aryl-4-Isoquinolinone Derivatives An Efficient Oxidative Preparation

References and Notes

• González-Cameno , A. M. , Badía , D. , Domínguez , E. , Urtiaga , M. K. , Arriortua , M. I. and Solans , X. S. 1994 . Tetrahedron , 37 : 10971 – 10982 .
   Google Scholar
• Hanna , P. E. , Grund , V. R. and Anders , M. W. 1974 . J. Med. Chem. , 17 : 1020 – 1023 .
   PubMed Web of Science ®Google Scholar
• Grethe , G. 1981 . Isoquinolines , 446 New York : Interscience .
   Google Scholar
• Armesto , D. , Ortiz , M. , Horspool , W. M. and Romano , S. 1995 . An. Quim. , 91 : 374 – 377 .
   Google Scholar
• Brossi , A. 1986 . The Alkaloids , Vol. 28 , 113 Orlando : Academic Press .
   Google Scholar
• Airapetyan , G. K. , Mikaelyan , A. P. , Markaryan , E. A. , Pogosyan , A. V. , Markaryan , K. Zh. and Oganesyan , Z. V. 1988 . Arm. Khim. Zh. , 41 : 629 – 634 . (CA, 111:39170r, 1989)
   Google Scholar
• For the application to the synthesis of benzo[c]phenanthridines see: Séraphin D. Lynch M. A. Duval O. Tetrahedron Lett. 1995 36 5731 5734 and references cited therein; Several heterobenzopirones were prepared from 4-isoquinolones in: Yangjun, L.; Liu, Y. Yingyong Huaxue 1995, 12, 116–117 (CA 123:339681m, 1995)
   Google Scholar
• Badía , D. , Domínguez , E. , Lete , E. and Villa , M. J. 1991 . Trends in Hetrocyclic Chemistry , : 2 – 11 . and references cited therein
   Google Scholar
• Oxidation to one simple 4-isoquinolone with moderate yield is described in: Gensler W. J. Lawless S. F. Bluhm A. L. Dertozous H. J. Org. Chem. 1975 40 733 739
   Google Scholar
• Bhakuni , D. S. , Gupta , P. K. , Joshi , P. P. and Gupta , S. 1982 . Indian J. Chem. , 21B : 389 – 392 . Protoberberine alkaloid ophiocarpinone, which is closely related to the target 3-aryl-4-isoquinolinone system, was obtained (MnO2 oxidation) with moderate yield in
   Google Scholar
• Sainsbury , M. , Brown , D. W. , Dyke , S. F. and Hardy , G. 1969 . Tetrahedron , 25 : 1881 – 1895 .
   Google Scholar
• Cava , M. P. and Noguchi , I. 1973 . J. Org. Chem. , 38 : 60 – 62 .
   Google Scholar
• Keirs , S. and Overton , K. 1987 . J. Chem. Soc., Chem. Commun. , : 1660 – 1661 .
   Google Scholar
• Liu , H-J. and Nyangulu , J. M. 1989 . Synth. Commun. , 19 : 3407 – 3411 .
   Web of Science ®Google Scholar
• Warnhoff , E. W. and Wildman , W. C. 1957 . J. Am. Chem. Soc. , 79 : 2192 – 2198 .
   Google Scholar
• San Martín , R. , Olivera , R. , Mtez de Marigorta , E. and Domínguez , E. 1995 . Tetrahedron , 51 : 5361 – 5368 .
   Google Scholar
• Tellitu , I. , Badía , D. , Domínguez , D. and García , F. J. 1994 . Tetrahedron: Asymmetry , 5 : 1567 – 1578 .
   Google Scholar
• Borch , R. F. and Hassid , A. I. 1972 . J. Org. Chem. , 37 : 1673 – 1676 .
   Web of Science ®Google Scholar
• Selected data for new N-methyl derivatives 3: (3R∗,4S∗)-6,7-Dimethoxy-3-(3,4-dimethoxyphenyl)-4-hydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline 3a., Rf (10% MeOH/CH2Cl2) 0.4; IR vmax 3490 (O-H); 1H NMR (250 MHz, CDCl3): δ 2.20 (3H, s, NMe), 2.28 (1H, bs, O-H), 3.32 (1H, d, J 6.6, H-3), 3.55 (1H, d, J 15.1, H-1pseudo-eq), 3.72 (1H, d, J 15.1, H-1pseudo-ax), 3.80 (3H, s, OMe), 3.87 (9H, s, OMe), 4.73 (1H, d, J 6.5, H-4), 6.55 (1H, s, H-8arom), 6.76–6.81 (3H, m, Harom), 7.01 (1H, s, H-5arom); 13C NMR (62.83 MHz, CDCl3): δ 43.2 (NMe), 55.8, 55.9 (OMe), 56.5 (C-1), 72.3, 72.9 (C-3, C-4), 108.1, 109.9, 110.8, 111.0, and 121.1 (Carom-H), 126.5, 128.5, and 130.3(C arom-C), 148.1, 148.5, 148.7, and 149.2 (Carom-O); m/z 359 (M+, 2), 180 (100), 165 (10), 151 (8); (Found: C, 67.01; H, 7.03; N, 3.77. C20H25NO5 requires C, 66.97; H, 7.01; N, 3.79%). (1R∗,3R∗,4S∗)-6, 7-Dimethoxy-1, N-dimethyl-4-hydroxy-3-phenyl-1,2,3,4-tetrahydroisoquinoline 3c, Rf (5% MeOH/CH2Cl2) 0.5; IR vmax 3500–3020 (O-H); 1H NMR (250 MHz, CDCl3): δ 1.44 (3H, d, J 6.4, C1Me), 2.32 (3H, s, NMe), 3.71 (1H, q, J 6.4, H-1), 3.89 (3H, s, OMe), 3.90 (3H, s, OMe), 3.96 (1H, d, J 5.0, H-3), 4.66 (1H, d, J 5.0, H-4), 6.64 (1H, s, H-8), 6.93 (1H, s, H-5), 7.11–7.28 (5H, m, Harom); 13C NMR (62.83 MHz, CDCl3): δ 18.9 (C1 CH3), 40.2 (NMe), 55.8, 55.9 (OMe), 56.6 (C-1), 68.6, 71.3 (C-3, C-4), 109.9, 110.7 and 127.7 (Carom-H), 127.8 (C arom-C), 128.3, 129.1 (Carom-H), 132.5, and 137.8 (C arom-C), 147.9 and 148.6 (Carom-O); (Found: C, 72.82; H, 7.42; N, 4.46. C19H23NO3 requires C, 72.80; H, 7.40; N, 4.47%); (1S∗,3R∗,4S∗)-1, N-Dimethyl-4-hydroxy-3-phenyl-6,7,8-trimethoxy-1,2,3,4-tetrahydroisoquinoline 3d, Rf (5% MeOH/CH2Cl2) 0.5; IR vmax 3600–3250 (O-H); 1H NMR (250 MHz, CDCl3: δ 1.39 (3H, d, J 6.3, C1Me), 2.23 (3H, s, NMe), 3.20 (1H, d, J 8.8, H-3), 3.82 (1H, q, J 6.3, H-1), 3.87 (6H, s, OMe), 3.93 (3H, s, OMe), 4.67 (1H, d, J 8.8, H-4), 6.94 (1H, s, H-5), 7.34–7.46 (5H, m, Harom); 13C NMR (62.83 MHz, CDCl3): δ 23.6 (C1 CH3), 41.9 (NMe), 55.6, 56.5, 56.5 (OMe), 60.4 (C-1), 71.7 (C-3), 72.6 (C-4), 102.7 (C arom-H), 124.4, (C arom-C), 127.6, 128.4 and 128.7 (Carom-H), 133.2, 140.7 (Carom-C), 141.5, 149.5 and 151.8 (Carom-O); (Found: C, 69.87; H, 7.30; N, 4.10. C20H25NO4 requires C, 69.93; H, 7.34; N, 4.08%); (1R∗, 3R∗, 4S∗)-1, N-Dimethyl-4-hydroxy-3-phenyl-6,7,8-trimethoxy-1,2,3,4-tetrahydroisoquinoline 3e, Rf (5% MeOH/CH2Cl2) 0.5; IR vmax 3500–3200 (O-H); 1H NMR (250 MHz, CDCl3): δ 1.37 (3H, d, J 6.4, C1Me), 2.18 (3H, s, NMe), 3.79 (1H, d, J 7.9, H-3), 3.83 (3H, s, OMe), 3.85 (3H, s, OMe), 3.93 (3H, s, OMe), 4.15 (1H, q, J 6.4, H-1), 4.76 (1H, d, J 7.9, H-4), 6.81 (1H, s, H-5), 7.33–7.36 (5H, m, Harom); 13C NMR (62.83 MHz, CDCl3): δ 14.7 (C1CH3), 39.6 (NMe), 54.7, 55.8 (OMe), 60.7 (C-1), 66.4, 72.4 (C-3, C-4), 105.6 (C arom-H), 126.8, (C arom-C), 127.9, 128.6 and 129.1 (Carom-H), 131.1, 139.7 (C arom-C), 141.2, 149.4 and 152.5 (Carom-O); (Found: C, 69.90; H, 7.38; N, 4.11. C20H25NO4 requires C, 69.93; H, 7.34; N, 4.08%); (1S∗,3R∗4S∗)-1,N-Dimethyl-4-hydroxy-3-(2-methoxyphenyl)-6,7,8-t rimethoxy-1,2,3,4-tetrahydroisoquinoline 3f, Rf (5% MeOH/CH2Cl2) 0.5; IR vmax 3500–3200 (O-H); 1H NMR (250 MHz, CDCl3): δ 1.38 (3H, d, J 6.3, C1Me), 2.22 (3H, s, NMe), 3.15 (1H, d, J 8.8, H-3), 3.83 (3H, s, OMe), 3.87 (6H, s, OMe), 3.88 (1H, q, J 6.3, H-1), 3.93 (3H, s, OMe), 4.64 (1H, d, J 8.8, H-4), 6.91–6.94 (3H, m, Harom), 7.36–7.37 (2H, m, Harom); 13C NMR (62.83 MHz, CDCl3): δ 23.4 (C1 CH3), 41.8 (NMe), 55.1, 55.2, 55.7, 55.8 (OMe), 60.6 (C-1), 71.7, 72.0 (C-3, C-4), 102.8, 114.0, 124.4, 129.9 (C arom-H), 132.5, 133.2 and 140.8 (C arom-C), 149.7, 141.2, 152.0 and 159.2 (Carom-O); (Found: C, 67.53; H, 7.20; N, 3.62. C21H27NO5 requires C, 67.52; H, 7.29; N, 3.75%)
   Google Scholar
• Fatialdi , A. J. 1986 . Organic Synthesis by Oxidation with Metal Compounds , 119 – 121 . New York : Plenum Press .
   Google Scholar
• Selected data for new dehydration and aromatization products 4, 5, and 6: 4: (85%), oil, Rf (5% MeOH/CH2Cl2) 0.5; IR vmax 3700 (O-H), 1630 (C=N); 1H NMR (250 MHz, CDCl3): δ 2.12 (1H, bs, O-H), 3.93 (6H, s, OMe), 3.94 (6H, s, OMe), 4.55 (dd, 1H, J 10.1, 2.4, H-3), 4.72 (1H, d, J 10.2, H-4), 6.85–6.92 (4H, m, Harom), 7.07 (1H, s, H-5arom), 8.30 (1H, s, H-1); 13C NMR (62.83 MHz, CDCl3): δ 55.8, 55.9, 56.1 and 56.2 (OMe), 68.4, 70.7 (C-3, C-4), 108.0, 110.1, 111.0, 111.1, and 120.1 (Carom-H), 120.5, 131.4, and 133.0 (C arom-C), 148.5, 148.8, 149.1, and 152.1 (Carom-O), 159.5 (C-1); (Found: C, 66.40; H, 6.20; N, 4.02. C19H21NO5 requires C, 66.44; H, 6.17; N, 4.08%). 6,7-Dimethoxy-1,2-dimethyl-4-hydroxy-3-phenylisoquinolinum salt 5: m.p. 74–75°C (diethyl ether), Rf (10% MeOH/CH2Cl2) 0.1; IR: vmax 3600–3300 (O-H); 1H NMR (250 MHz, CDCl3): δ 3.46 (3H, s, C1CH3), 4.09 (3H, s, OMe), 4.14 (3H, s, OMe), 4,31 (3H, s, NMe), 7.35 (1H, s, H-8arom), 7.63–7.41 (5H, m, Harom), 7.81 (1H, s, H-5arom); (Found: C, 73.55; H, 6.47; N, 4.52. C19H20NO3 requires C, 73.51; H, 6.49; N, 4.51%). 6.7-Dimethoxy-1,2-dimethyl-3-phenyl-1,2-dihydroisoquinoline 6: oil, Rf (5% MeOH/CH2Cl2 0.7; IR vmax 1510 (C=C); 1H NMR (250 MHz, CDCl3): δ 1.28 (3H, d, J 6.7, C1CH3), 2.66 (1H, s, NMe), 3.89 (6H, s, OMe), 4.24 (1H, q, J 6.7, H-1), 5.94 (1H, s, H-4), 6.60 (1H, s, H-8arom), 6.66 (1H, s, H-5arom), 7.32–7.58 (5H, m, Harom); 13C NMR (62.83 MHz, CDCl3): δ 19.9 (C1 CH3), 39.4 (NMe), 55.8, 56.1 (OMe), 58.8 (C-1), 104.6, 107.0, and 109.1 (Carom-H, C-4), 125.1, 125.4 (C arom-C, C-3), 127.6, 127.8, and 128.(Carom-H), 138.1, 144.6, 147.4, and 148.0 (C arom-C, Carom-O); (Found: C, 77.30; H, 7.17; N, 4.65. C19H21O2N requires C, 77.25; H, 7.17; N, 4.65%).
   Google Scholar
• Fetizon , M. , Gomez-Parra , F. and Louis , J. M. 1976 . J. Heterocycl. Chem. , 13 : 525 – 528 . Ag2CO3 on Celite oxidative transformation of dihydrocodeine into dihydrocodeinone is described in
   Google Scholar
• Increasing number of applications for Dess-Martin periodinane are described in: Dess D. B. Martin J. C. J. Am. Chem. Soc. 1991 113 7277 7287
   Web of Science ®Google Scholar
• Application of Swern oxidation in the field of isoquinoline alkaloids is reported in: Tidwell T. T. Synthesis 1990 857 870
   Web of Science ®Google Scholar
• Wasserman , H. H. and Amici , R. M. 1989 . J. Org. Chem. , 54 : 5843 – 5844 .
   Web of Science ®Google Scholar
• Broka , C. A. and Gerlits , J. F. 1988 . J. Org. Chem. , 53 : 2144 – 2150 .
   Google Scholar
• Walts , A. E. and Roush , W. R. 1985 . Tetrahedron , 41 : 3463 – 3478 .
   Web of Science ®Google Scholar
• Ibuka , T. , Konoshima , T. and Inubushi , Y. 1975 . Chem. Pharm. Bull. , 23 : 133 – 138 .
   Google Scholar
• Gainelli , G. and Gordillo , G. 1984 . Chromium Oxidations in Organic Chemistry , 132 – 144 . Berlin : Spring-Verlag .
   Google Scholar
• Corey , E. J. and Suggs , J. W. 1975 . Tetrahedron Lett. , : 2647 – 2650 .
   Web of Science ®Google Scholar
• Corey , E. J. and Schmidt , G. 1980 . Tetrahedron Lett. , 21 : 731 – 734 .
   Google Scholar
• The stereochemistry of the new isoquinolinones 2a-d was determined by NOE experiments: Kinss M. Sanders J. K.M. J. Magn. Res. 1984 56 518 523
   Google Scholar
• Hall , D. L. and Sanders , J. K.M. 1980 . J. Am. Chem. Soc. , 102 : 5703 – 5711 . NOE effect was observed between the methyl group at C-1 and H-3. In addition, no NOE can be seen between H-1 and H-3 protons
   Web of Science ®Google Scholar
• Harcourt , D. N. , Hussain , F. , Taylor , N. and Nasir , M. 1986 . J Chem. Soc., Perkin Trans. I , : 1329 – 1338 .
   Google Scholar
• Ireland , R. E. and Schicss , P. W. 1960 . Tetrahedron Lett. , : 37 – 43 .
   Google Scholar